Higher Degree by Research Candidate
School of Biomedicine
Faculty of Health and Medical Sciences
Yu Chinn Joshua Chey is a molecular biologist and higher degree by research candidate. He is currently undertaking a PhD in the School of Biomedicine at the University of Adelaide, supervised by Prof. Paul Thomas and Dr. Fatwa Adikusuma.
Joshua is passionate about the biology and etiology of presently incurable diseases. His current project aims to develop CRISPR/Cas9 gene editing strategies for the curative treatment of monogenic disorders.
A CRISPR cure for Duchenne Muscular Dystrophy
CRISPR/Cas9's therapeutic potential is, without a doubt, incredibly powerful. This cutting-edge gene-editing technology enables fast, precise, and straightforward modification of DNA. It has quickly become the mainstay technique of many research laboratories to manipulate the genome of cells and laboratory animals. There is currently significant research interest in transitioning the use of CRISPR/Cas9 to the clinic and further developing it as therapy for the permanent correction of many different genetic diseases.
Joshua's PhD project involves developing CRISPR/Cas9 editing strategies to permanently correct Duchenne Muscular Dystrophy (DMD). DMD is a severe muscle-wasting disease associated with mutations to the DMD gene located on the X-chromosome. Due to loss-of-function mutations to the DMD gene, patients do not express functional dystrophin protein- an essential membrane stabiliser in striated muscles. Muscle contractions cause damage to the unstable muscle cell membrane, leading to necroptosis and subsequent replacement of muscle with fibrous and fat tissue, manifesting in the progressive loss of muscle strength observed in patients. This disease is ultimately fatal as patients succumb to complications arising from heart and respiratory weakness.
Our CRISPR therapy team is focused on developing CRISPR/Cas9 editing strategies that are safe, effective, and applicable for human DMD patients. Joshua is involved in identifying, testing and tuning strategies that apply to a broad range of DMD mutations, with hopes of identifying the best candidates for further testing in a clinical setting. These strategies intend to permanently change and correct the sequence of patients' DMD gene to restore dystrophin protein expression and halt disease progression.
Joshua is also actively involved in side projects relating to the advancement of CRISPR/Cas9 technology and novel PRIME editing technology.
Sn'HIF'fing out roles for HIFs in Multiple Myeloma
Joshua's MPhil project is in the areas of hypoxia (state of low oxygen levels) and blood cancer biology. Cellular responses to hypoxia are primarily mediated by the HIFs, which play important roles in both normal physiology and in disease, such as in cancer, infarction and inflammation. While hypoxia is widely recognised as a hallmark of solid tumours, its role in the pathology of liquid tumours is less well understood.
MM is the second most common blood cancer, an incurable haematological malignancy of bone marrow plasma cells that manifests as combination of clinical symptoms known mnemonically as CRAB: hyperCalcaemia, Renal failure, Anaemia, and Bone lesions. As the bone marrow microenvironment is physiologically hypoxic, HIF activation is likely to to contribute to the unfavourable biology of MM through the induction of angiogenesis, metastasis, osteolysis and cell survival.
Using cutting-edge CRIPSR/Cas9 technology, Joshua aims to elucidate HIF's roles in MM pathology to strengthen the rationale for the development of MM therapies that target the hypoxic bone marrow niche and for the repurposing of HIF-inhibitors.
In addition to his interests in MM hypoxia, Joshua is also interested in the study of HIF pathway components in both normal and disease biology. He is actively involved in side projects pertinent to the study of Factor Inhibiting HIF (FIH) as a novel regulator of metabolism and the study of HIFs in retinal metabolism.
Awards and Achievements
Date Type Title Institution Name Country Amount 2021 Scholarship Ian Wilson Liberal Research Supplementary Scholarship The University of Adelaide Australia — 2020 Scholarship Adelaide Graduate Research Scholarship The University of Adelaide Australia — 2019 Scholarship School of Biological Sciences Short Term Scholarship The University of Adelaide Australia — 2018 Award Most Outstanding Student Poster: Runner Up Australia and New Zeland Society for Cell and Developmental Biology Inc. Australia — 2017 Scholarship Master of Philosophy (No Honours) International Scholarship 2017 The University of Adelaide Australia — 2017 Award The RA Fisher Prize for Genetics II 2016 The University of Adelaide Australia — 2015 Scholarship Adelaide Summer Research Scholarship 2015 The University of Adelaide Australia — 2014 Award Outstanding Academic Achievement Award 2014, 2015, 2016, 2017 The University of Adelaide Australia —
Language Competency English Can read, write, speak, understand spoken and peer review Malay Can read, write, speak and understand spoken
Date Institution name Country Title 2020 University of Adelaide Australia Doctor of Philosophy 2017 - 2020 University of Adelaide, Adelaide Australia Master of Philosophy 2014 - 2017 University of Adelaide, Adelaide Australia Bachelor of Science (Biomedical Science)
Year Citation 2021 Adikusuma, F., Lushington, C., Arudkumar, J., Godahewa, G. I., Chey, Y. C. J., Gierus, L., . . . Thomas, P. Q. (2021). Optimized nickase- and nuclease-based prime editing in human and mouse cells.. Nucleic acids research, 49(18), 10785-10795.
2018 Sim, J., Cowburn, A. S., Palazon, A., Madhu, B., Tyrakis, P. A., Macias, D., . . . Johnson, R. S. (2018). The Factor Inhibiting HIF asparaginyl hydroxylase regulates oxidative metabolism and accelerates metabolic adaptation to hypoxia. Cell Metabolism, 27(4), 898-e.7.
DOI Scopus29 WoS28 Europe PMC15
— Adikusuma, F., Lushington, C., Arudkumar, J., Godahewa, G. I., Chey, Y. C. J., Gierus, L., . . . Thomas, P. Q. (n.d.). Optimized nickase- and nuclease-based prime editing in human and mouse cells.
Year Citation 2019 Chey, Y. C. (2019). Generation and Transcriptomic Analysis of HIF-1Alpha and HIF-2Alpha Knockout 5TGM1 Multiple Myeloma Cells. (Master's Thesis).
Date Role Membership Country 2021 - 2022 Member Australian Society for Medical Research Australia 2018 - 2023 Member Australia and New Zealand Society for Cell and Developmental Biology Australia 2017 - 2022 Member Australian Society for Biochemistry and Molecular Biology Australia
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